Albany Medical Review - August 2001

Case Report -
A 32-year-old man with rash and a fever

Hamish Kerr, MD

A 32-year-old white male presents to an Emergency Department with a rash for three days, first noticing it on his arms, then his trunk. It is itchy, though not intolerable and he has scratched some areas. He has not had such a rash before. The day after the rash begins he has onset of fever. His temperature is as high as 103; he is not experiencing chills.

His past medical history is unremarkable. He has had no surgeries and does not take any medications. He denies using any OTC medicines. He has no medication allergies. He lives with his daughter and partner and is an ex-marine. He saw no active service. He was stationed at various locations around the country, but denies foreign deployment. His parents live in California. He was last there in December. He does not smoke, though he has chewed tobacco for fifteen years, and his alcohol intake is minimal. He denies the use of illicit drugs. He has two sisters and a brother who are all well. He was working at an elementary school the week prior to presentation. He recounts that there was an outbreak of chicken pox at the school recently. He, however, has little contact with the school children as his duties are mainly janitorial. He is exposed to dusty environments at work, particularly when cleaning out the basement. What makes this even more unpleasant is the occasional rat carcass he has to take care of down there.

On exam he is a solidly built male with tattoos on his torso who is in no acute distress. He has a blood pressure of 132/80, a regular pulse of 60, a respiratory rate of 14 and a temperature of 98.5° F (36.9 C). He has a discrete erythematous macular eruption on his upper extremities and the front of his chest. There are excoriated areas on his lower arms. He has no conjunctival erythema or scleral icterus and his cranial nerve examination is normal. His oropharynx is unremarkable; his neck is supple with no lymphadenopathy. His precordium shows a PMI in the 5^th intercostal space in the mid-clavicular line with S1 & S2 present on auscultation. There are no additional sounds. His lungs are clear. His abdomen is soft and non-tender without hepatosplenomegaly. Bowel sounds are present. He has erythema in his groin creases without satellite lesions. His genitalia are normal. He has a normal neurological exam and no clubbing, cyanosis or edema of his extremities.

The patient is discharged from the Emergency Department and given Lotrimin cream for his groin rash and Benadryl for the itch. He continues to have fevers over the next couple of days and his rash becomes more prominent. Six days into the illness he begins to have some throat discomfort. This worsens to the extent he is eating less due to pain on swallowing. He also begins to feel worse with generalized aches and pains. On the seventh day after the onset of the rash he has deteriorated to the extent that his girlfriend brings him to the Emergency Department again.

His girlfriend says he has been taking very little orally since the day before. He has been lying on the couch in their apartment for two days and has felt very fatigued with minimal activity. He still denies chills or rigors. He is complaining of myalgias and headaches at this time. On further questioning, he says his immunizations are up to date. He did not have chicken pox as a child. He denies any recent outdoor activity. Nobody he knows has had similar symptoms lately. He professes to a monogamous sexual relationship with his girlfriend. He denies nausea, diarrhea, night sweats, dysuria, cough, chest pain, dyspnea or pain anywhere other than his throat.

On examination he is lying quietly with his eyes closed. His blood pressure is 130/82, pulse 78, respiratory rate 16 and temperature 101° F. When opening his eyes he experiences photophobia. His neck feels stiff. He does not experience neck stiffness on Brudzinski nor Kernig manipulations. There is no papilloedema on fundoscopy. His conjunctivae are slightly erythematous; he has significant pharyngeal erythema with several one to two mm. shallow ulcerations of the oral mucosa. There are no exudates or petechiae. He has dry, cracked lips and clear nares. His tympanic membranes are unremarkable; he has neither facial tenderness, nor lymphadenopathy on palpation of his neck. The erythematous eruption now involves his face and scalp as well as his arms and torso (front and back). There are some lesions on his lower extremities but none on his palms or soles. The lesions now have a maculopapular character, without any vesicles or crusting. All the lesions appear to be of similar age. His exam is otherwise unchanged.

The patient has labs drawn.

How would you proceed with this man’s management?

Fever and rash syndromes bring to mind several important systemic infections. In contrast to his initial presentation to the Emergency Department, the patient now appears systemically ill. Streptococcal & Staphylococcal Toxic Shock are associated with striking cutaneous findings, hypotension and symptoms localized to the site of infection. This patient is normotensive and has not localized symptoms to any extent. There is a clear concern about meningitis with headache, photophobia and neck stiffness.

Meningococcemia would be one consideration. Certainly Neisseria meningitidis can present with macular rash. Petechial or purpuric skin eruptions are classically associated with infection with this organism, which usually has a rapid course. Purpuric skin lesions have been noted in 50 to 90% of patients with fulminant meningococcemia². The fact that this man has had his illness for seven days makes meningococcus less likely.

However, there is a clinical entity known as chronic meningococcemia. This rare disease has a constellation of intermittent or sustained fevers, recurring maculopapular, nodular or petechial eruptions, and migratory arthritis or arthralgias with systemic toxicity. Pale to pink-colored macules and papules are seen in 40% cases. Small, irregularly round, subcutaneous hemorrhages with bluish-gray center containing pus are a distinctive lesion of this syndrome. They tend to appear in showers associated with onset of fever.

Encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae can mimic the presentation of Meningococcus.

Disseminated gonococcal infection follows untreated mucosal infection with N. gonorrhoeae in about 0.5 to 3% of patients. Skin lesions occur in 50 to 70%; the eruption typically appearing during the 1^st days of symptoms and recurring with each bout of fever. Tiny red papules or petechiae most commonly involve distal extremities with sparing of scalp, face, trunk and oral mucous membranes.

The patient’s meningeal symptoms and signs prompted an urgent lumbar puncture.

The lumbar puncture helps to exclude a bacterial etiology. Bacterial meningitis typically causes a turbid appearance to the CSF, a predominance of polys with high CSF white count in the 1000/mm³ range, a glucose level less than ²/₃ of serum glucose and a protein count of 1-5 g/dl.

Viral exanthems do not typically present with systemic illness. Meningitis can be a complication of measles. The rash in measles is generally macular, with pathognomonic Koplik spots on the buccal mucosa. The rash often begins behind the ears and becomes confluent as it spreads down the body.

Rickettsial infections typically begin with fever, chills, headache, generalized weakness and myalgias. The rash develops on an average of four days into the illness. Infection is usually conveyed to man through the skin from excreta of arthropods, but the saliva of some biting vectors can be infected.

Rocky Mountain Spotted Fever is the most common rickettsial disease in the USA. It has an Ixodus tick vector and 2-12% mortality if untreated. It is widely distributed through western and southeastern states. It has been reported in New York City ⁵. Most commonly the rash begins on the extremities, often around the wrists and ankles and spreads centipetally to the trunk in 24-48 hours. In only 10% of cases the rash begins on the trunk. Characteristically it affects the palms and soles in the later stages of the illness. It is rarely urticarial or pruritic.

Ehrlichiosis may be clinically indistinguishable from RMSF. Ticks carried by white-tailed deer and white-footed mice spread it. It usually affects older people than RMSF does and is most common from April through September. The rash is less common than in RMSF. Human granulocytic ehrlichiosis is prevalent in Wisconsin, Minnesota, Connecticut and New York and is associated with E. phagocytophilia. Human monocytic ehrlichiosis due to E. chaffeensis is prevalent in South East and South Central USA.

Epidemic Typhus is caused by R. prowazeki and is transmitted by infected feces of the human body louse, Pediculus humanus corporis, usually through scratching the skin, or sometimes by inhalation. Patients suffering from epidemic typhus infect the lice, who leave when the patient is febrile. A maculopapular rash typically starts on the trunk and progresses centrifugally. It appears on the fourth to sixth day and often resembles measles. In early stages it is blanching, but soon becomes petechial with subcutaneous mottling. The neck and face are seldom affected. During the second week of illness the CNS becomes involved and apathy and dullness become manifest, often progressing to delirium and coma. The disease is prevalent in parts of Africa, South America and Afghanistan. Mortality is about 40%.

Endemic typhus or Murine typhus is caused by R. mooseri or R. typhi and is endemic worldwide. Man is infected when, by scratching, he introduces the feces or contents of a crushed flea, Xenopsyll cheopis, which has fed on an infected rat. Inhaling infected aerosols containing contaminated flea feces or contaminating mucous membranes with infectious excreta are also proposed mechanisms of infection. The symptoms resemble those of a mild epidemic typhus. Fatalities are rare and CNS disease damage is generally much less extensive. The nonspecific clinical manifestations of murine typhus preclude a clinical diagnosis. Epidemiological considerations are therefore essential for identifying the cause of the disease. In the USA, residence in an endemic area and possible exposure to rodents provide important clues ⁶.

Rickettsialpox (R.akari) presents in a similar manner. The acute illness may have a primary local lesion, known as an eschar, which goes on to ulcerate and form a black scar by fifth or sixth day. This is the site of the mouse mite vector bite. Anorexia, photophobia, headaches and myalgias are prominent features. A papulovesicular rash develops one to ten days after the eschar appears and lasts for several weeks. The common house mouse is R. akari’s natural host and the mite Liponyssoides sanguineus transmits it. Northeastern USA, Ohio, and Utah are the areas with the highest prevalence. It is usually a self-limited disease without complications.

Our patient’s history of exposure to rat corpses in a dusty environment makes Murine Typhus or Rickettsialpox possibilities. He denied any recent tick exposure. Despite a negative lumbar puncture he had clinical evidence of CNS involvement with prominent photophobia at presentation. This is most in keeping with Epidemic Typhus or Murine Typhus. His rash developed from his extremities to his trunk, more consistent with RMSF. He did have a couple of lesions that looked suspiciously like eschar on careful examination. His rash persisted for greater than three weeks.

How could these clinical suspicions be confirmed?

Rickettsial illness is investigated with the Weil-Felix reaction. This is a nonspecific agglutination of the somatic antigens of non-motile Proteus species by the patient’s serum. A four-fold rise in titer is diagnostic. Complement fixation, microagglutination and fluorescence may detect species-specific antibodies. Rickettsiae may be isolated from the blood in the first week of illness by intra-peritoneal inoculation into male guinea pigs or mice.

By visualizing R.akari in a skin-biopsy specimen, Kass et al demonstrated the value of immunohistologic analysis in the diagnosis of rickettsialpox ⁴. Skin biopsy has a sensitivity of approximately 70% when performed and interpreted appropriately. This sensitivity should be compared with sensitivity of serological tests, which are diagnostic in less than 20% of patients during the acute stage of the illness ⁴.

It is widely accepted that the current reporting system for RMSF and Murine Typhus results in the underestimation of the true incidence of these infections by a factor of at least four.

Treatment of rickettsial infection with doxycycline 100mg IV or PO every 12 hours for 14 days is recommended. Chloramphenicol 1g IV every 6 hours, also for 14 days, is an alternative.

1. The Washington Manual of Medical Therapeutics, 29^th Edition, Lippincott Williams & Wilkins.

2. Mandell: Principles and Practice of Infectious Diseases, 5^th ed., Churchill Livingstone.

3. Davidson’s Principles and Practice of Medicine, Seventeenth Edition, Churchill Livingstone.

4. Kass et al. Rickettsialpox in a New York City Hospital, 1980 to 1989 NEJM Dec15, ’94 Vol. 331, No.24.

5. Walker & Dumler Editorial: Emerging and Reemerging Rickettsial Diseases NEJM Dec15, ’94Vol.331, No. 24.

6. Rickettsia pp1645 VII Microbial Agents

Albany Medical Center
43 New Scotland Avenue
Albany, New York 12208

E-mail the AMC Webmaster: Webmaster@mail.amc.edu

See your health care provider for specific medical advice.
AMC takes no responsibility for content  provided at external link sites.
Copyright, 1999-2001, Albany Medical Center.  All Rights Reserved